Dental caries is an infectious disease caused by Streptococcus mutans. Despite fluoridation and improved Dental hygiene in industrialized countries, worldwide Dental cades is still a significant public health problem affecting 50-90 percent of the population 0Nodd Health Organization). In the United Sates of America, 59 percent of first graders have at least one cavity, one third of the adult population does not see a Dentist annually, and 24 percent of the elderly experience caries-associated tooth loss (Oral Health America). Animal studies demonstrated that this disease was preventable by immunization with so mutans antigens. Gene cloning technology was applied to produce recombinant bacteria, protein and peptide vaccines for active immunization, and antibody for passive immunization. Various levels of protection were achieved with these vaccines. Considering that the population at risk is mostly from low socioeconomic groups (Surgeon General's report, U.S. DHHS, 2000), it is desirable to find means to lower the costs of vaccine production for mass immunization. One possibility is to directly immunize with a plasmid DNA (cDNA) containing the gene(s) of interest and obtain expression of the target protein(s) in the host. Thus, expensive protein isolation from recombinant clones is avoided. The Long Term Goal of the current study is to prepare an efficacious, safe and economical Dental Cades vaccine. The Specific Aim for the proposed period is to explore the prospect of a DNA vaccine against S. mutans with special emphasis on comparing the efficacy, duration and costs with those of corresponding Protein Vaccine. As models, the S. mutans antigen A (AgA), a recognized candidate vaccine antigen, and its precursor the wall-associated protein A (WapA), a factor involved in colonization and buildup of Dental plaque, will be used. The work proposed is supported by the availability of the recombinant clones needed for the production of WapA and AgA protein vaccines, and wapA-pDNA and agA-pDNAvaccines, and by the expression of WapA and AgA in mammalian cells transfected with these pDNA constructs. The results obtained will determine the feasibility and cost-effectiveness of genetic immunization against Dental caries, and the work performed will serve as a model for vaccine research against other infectious agents invading the body through mucosal surfaces. [unreadable] [unreadable]